The associations between tricarboxylic acid cycle metabolites, and risk of major adverse cardiovascular events in acute coronary syndrome

Funding Acknowledgements Type of funding sources: None. Background Cardiovascular disease and acute coronary syndrome (ACS) are one of the main causes of morbi-mortality caring a high health cost due to its consequences. Prognostic stratification in patients admitted with an acute coronary syndrome (ACS) is necessary to providing efficient follow-up and guiding intensive treatment to those at high risk of adverse cardiovascular events. Is crucial to identifying new molecular pathways to predict those patients with worst prognosis and find new molecular targets. Purpouse The aim of the study is to investigate the relation between TCA cycle disturbance and cardiovascular diseases. Methods In this prospective cohort study, we included 309 patients with ACS. During a mean follow-up of 6.7 years, 131 patients developed major adverse cardiovascular events (MACE) (myocardial infarction, hospitalization for heart failure, and all-cause mortality). Plasma concentrations of TCA cycle metabolites were profiled by liquid chromatography tandem mass spectrometry. Hazard ratios were estimated with multivariable Cox regression models. Results After adjustment for traditional cardiovascular risk factors and medications, participants in the highest tertile vs. the lowest tertile of baseline Isocitrate concentrations had a higher risk of MACE [(HR: 1.25; 95% CI: 1.03, 1.5) However, these associations were no longer significant, after additional adjustment for eGFR. eGFR mediated the associations of Isocitrate (75 %) No significant associations were found for other TCA metabolites. Conclusions High plasma TCA metabolites concentrations are related to the risk of developing MACE during the follow-up and this relationship is substantially mediated by renal function. Understanding the potential interplay of TCA metabolite’s renal function, and incident MACE, may contribute to novel prevention and treatment efforts in ACS.